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JAC Advance Access originally published online on October 20, 2006
Journal of Antimicrobial Chemotherapy 2006 58(6):1307; doi:10.1093/jac/dkl417
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Correspondence

Comment on: Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus

Houssem Hmouda1,*, Chaker Ben Salem2, Kamel Bouraoui2 and Letaief Jemni3

1 Medical Intensive Care Unit and Emergency Department, Sahloul University Hospital Sousse, Tunisia 2 Department of Clinical Pharmacology, Faculty of Medicine of Sousse Tunisia 3 Clinique les Oliviers Sousse, Tunisia


*Corresponding author. Tel: +216-98-481-287; Fax: +216-73-367-451; E-mail: houssem_hmouda{at}yahoo.com

Keywords: microbial infections , trimethoprim/sulfamethoxazole , antibiotics , MRSA

Sir,

We read with great interest the article written by Kaka et al.1 in the September 2006 issue of JAC. The authors clearly demonstrated that trimethoprim/sulfamethoxazole is rapidly bactericidal against methicillin-resistant Staphylococcus aureus (MRSA) in vitro when compared with most other orally available antimicrobials. No antibiotic combination exhibited better killing than trimethoprim/sulfamethoxazole alone. Furthermore, activities against community-acquired (CA) MRSA and hospital-acquired (HA) MRSA were similar.

We are reassured with this conclusion, which corroborates our clinical findings in Tunisia published 13 years ago.2 In our previously published series trimethoprim/sulfamethoxazole was administered for treatment of infections due to MRSA in 27 patients with the following infections: soft tissue (n = 15), renal carbuncle (n = 3), arthritis (n = 2), spondylodiscitis with psoas abscess (n = 1), meningitis (n = 1), prosthetic valve endocarditis (n = 1) and bacteraemia (n = 4). Trimethoprim/sulfamethoxazole was administered orally at daily doses of trimethoprim 320–480 mg, and sulfamethoxazole 1600–2400 mg. Trimethoprim/sulfamethoxazole plus rifampicin was used in eight patients. Patients with polymicrobial soft-tissue infections received penicillin G and/or metronidazole in addition to trimethoprim/sulfamethoxazole. Twenty-six patients were cured; one patient with bacteraemia and osteitis was not cured due to the emergence of resistance. Trimethoprim/sulfamethoxazole was well tolerated by all patients.

In fact, we were not the only clinicians to remind readers about the efficacy and safety of trimethoprim/sulfamethoxazole in the treatment of MRSA infections. Since the early 1970s, the efficacy of trimethoprim/sulfamethoxazole in severe S. aureus infections has been reported, particularly for endocarditis, bacteraemia, meningitis, and bone and joint infections.3 However, failures during treatment with trimethoprim/sulfamethoxazole have also been reported.

Based on the findings of Kaka et al., adding rifampicin to trimethoprim/sulfamethoxazole showed a trend towards antagonism in vitro. However, in our series all patients (n = 8) treated with this combination were cured. We were not surprised by these results since in vitro antagonism does not necessarily imply failure of treatment. Nevertheless, confirmation of efficacy of rifampicin–trimethoprim/sulfamethoxazole in vivo needs further investigation before being recommended for severe infections. Therapeutic options that have a potential fluoroquinolones-sparing effect are well appreciated. Indeed, curtailing the use of fluoroquinolones could be beneficial, since increasing epidemiological, pharmacological and biological evidence incriminate this antibiotic class as an important risk factor for the acquisition and dissemination of MRSA.4,5

Therefore, it is urgent for the worldwide medical community to reexamine the clinical efficacy of older active therapies, such as trimethoprim/sulfamethoxazole, for treating severe infections due to MRSA. It is mandatory to conduct trials that compare agents such as linezolid or vancomycin with trimethoprim/sulfamethoxazole for the treatment of MRSA. This comparison is justified by the low cost of trimethoprim/sulfamethoxazole, its adequate oral bioavailability and its potential vancomycin-sparing effect. Any new recommendation on the use of trimethoprim/sulfamethoxazole should be based on strong evidence rather than sporadic case reports or in vitro studies. The modalities of treatment (dose, duration), adverse effects, cure rates and failure should be clarified.

Transparency declarations

We declare that we have no conflict of interest.

References

1 Kaka AS, Rueda AM, Shelburne SA III, et al. (2006) Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 58:680–3.[Abstract/Free Full Text]

2 Jemni L, Hmouda H, Letaief A. (1994) Efficacy of trimethoprim/sulfamethoxazole against clinical isolates of methicillin-resistant Staphylococcus aureus: a report from Tunisia. Clin Infect Dis 19:202–3.[Web of Science][Medline]

3 Adra M and Lawrence KR. (2004) Trimethoprim/sulfamethoxazole for treatment of severe Staphylococcus aureus infections. Ann Pharmacother 38:338–41.[Abstract/Free Full Text]

4 Weber SG, Gold HS, Hooper DC, et al. (2003) Fluoroquinolones and the risk of methicillin-resistant Staphylococcus aureus in hospitalized patients. Emerg Infect Dis 9:1415–22.[Web of Science][Medline]

5 Bisognano C, Vaudaux P, Rohner P, et al. (2000) Induction of fibronectin-binding proteins and increased adhesion of quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin. Antimicrob Agents Chemother 44:1428–37.[Abstract/Free Full Text]


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This Article
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58/6/1307    most recent
dkl417v1
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